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It has been the hope of science that advancements in genetics can translate into improvements in clinical care. Clinicians have always wished for a test or marker that can tell them which medication to use or not to use. For over a half century, research into the pharmacogenetic impact of psychiatric medications has shown that there are clear genetically determined pharmacokinetic and pharmacodynamic factors that impact treatment response - particularly in the area of antidepressants. Back in 1998, Smeraldi was the first to demonstrate that individuals with certain genetics ((l-allele l/l and l/s) had a better response to SSRI antidepressants than others (s-variat sls). This was replicated by a number of subsequent studies showing that neurotransmitter proteins contain genetic polymorphisms that alter their interaction with psychotropic drugs and contribute to response variability. This knowledge can be used to predict clinical results and adverse reactions.
Researchers from Stanford University, Department of Psychiatry have moved a little closer toward making this wish a reality. The goal of a recent study in the American Journal of Psychiatry was to identify genetic markers for antidepressant medication intolerance (pharmacokinetic effect). Variation in genes encoding serotonin receptors could also explain antidepressant side effects (pharmacodynamic effect). They did an 8-week, double-blind, randomized pharmacogenetic to compare a widely prescribed antidepressants (selective serotonin reuptake inhibitor [SSRI]) with a non-SSRI in 246 elderly patients with major depression.
Genotypes were determined for specific areas that had been previously associated with psychotropic medication treatment outcome. Clinical outcomes included treatment discontinuations, adverse events, medication compliance, and change in mood. Results showed a significant linear relationship between the number of C alleles and the probability of discontinuation and side effects in this group were greater for the SSRI with no effects on the non-SSRI antidepresant.
The researchers conclude that pharmacodynamic differences among patients due to variant 5-HT2A receptors appear to be more important than pharmacokinetic variation in determining the SSRI intolerance. Pharmacogenetic markers may be useful in predicting antidepressant treatment outcome.
A valuable and interesting outcome of genetic studies (Kim 2000) of these receptors has pointed to contrasing results that have been reported in some Asian populations. These results show that there was a difference in response in this population that suggests that this can only be attributed to ethnic differences. Clinicians need to be more aware of such studies and the impact that it can have on their day-to-day practice.
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